Epidemiology

Kamuzu University Of Health Sciences, Blantyre

Investigators

Abstract

Although the global malaria burden declined steadily from 2010 to 2015, progress has since stalled. To combat this stagnation, novel malaria control interventions have been introduced. New long-lasting insecticidal nets (LLINs) have been developed to ameliorate the problem of increasing insecticide resistance. The newly approved RTS,S vaccine is now being given in Malawi during the first two years of life, when disease is most severe and potentially life threatening. Measuring the combined impact of these two interventions on the full spectrum of malaria epidemiology (P. falciparum infection, uncomplicated clinical malaria, severe malaria disease), will provide new information on the real-world effectiveness of both interventions, and enhance understanding of the interplay of exposure and development of naturally acquired immunity. In this project, we will take advantage of unique access to sites where programmatic RTS,S vaccination has been on-going for five years, and mass distribution of dual-AI LLINs will also occur. We will build on the evaluation framework of the WHO-sponsored RTS,S implementation trial, our prior ICEMR studies, and links to detailed entomologic surveillance in the Transmission project. Using enhanced surveillance data from health centers and hospitals, we will quantify the population-level effects of RTS,S vaccination and dual-AI LLINs at scale. Longitudinal and case-control data will support more detailed investigation of individual-level impacts. All data collection will flank the 2026 dual-AI LLIN mass distribution campaign to facilitate analysis on the effects. Investigations are proposed in 3 Aims: 1) To measure changes in uncomplicated clinical malaria incidence, we will determine the overall and age-specific incidence of clinical malaria using enhanced health center surveillance in health centers where RTS,S vaccine became available in 2019, in 2022, and where vaccine has not been introduced. 2) To evaluate the impact of RTS,S vaccination and dual-AI LLINs on P. falciparum infection and transmission, we will conduct repeated household-based community surveys in the catchment areas of health centers with varied access to RTS,S vaccination. Thereby, we will assess vaccine timeliness and coverage and measure prevalence of Pf infection and gametocytemia in children aged 6-months to 10-years. 3) To assess changes in the epidemiology of severe malaria in response to RTS,S vaccination, we will conduct hospital surveillance to measure population-level and age-group specific incidence, and use a case-control study to quantify individual-level outcomes based on verified vaccine status. These population and individual-level results will characterize the epidemiologic consequences of the new interventions and be used to model their public health value at the national level. Results will provide new insights into the effectiveness of the RTSS,S vaccine in combination with dual-AI LLINs to prevent Pf infection, uncomplicated clinical malaria, and severe disease in the target age group, and its potential impact on older children. Ultimately, our results will help determine the potential contribution of these two new interventions in reestablishing progress toward malaria control and eventual elimination.